Partner and Localizer of BRCA2

Alternative Names

  • PALB2
  • FANCN Gene
  • FANCN
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OMIM Number

610355

NCBI Gene ID

79728

Uniprot ID

Q86YC2

Length

38,178 bases

No. of Exons

14

No. of isoforms

1

Protein Name

Partner and localizer of BRCA2

Molecular Mass

131295 Da

Amino Acid Count

1186

Genomic Location

chr16:23,603,160-23,641,337

Gene Map Locus
16p12.2

Description

PALB2 encodes a critical DNA repair protein that may be involved in tumour suppression. PALB2 functions by binding to and co-localizing with BRCA2, thereby permitting its stable intra-nuclear accumulation and preventing its proteasome-mediated degradation. The association of PALB2 with BRCA2 is critical as BRCA2 is essential for homologous recombination repair and tumour suppression. PALB2 also serves as the molecular scaffold in the formation of the BRCA1-PALB2-BRCA2 complex.

Mutations in the PALB2 gene impair its function and therefore its ability to carry out DNA repair. This results in a build-up of inter-strand crosslinks ultimately stalling DNA replication and causing either abnormal cell death or uncontrolled cell growth. Abnormal cell death leads to blood cell shortage and manifests as Fanconi anaemia while uncontrolled cell growth develops into cancers. Hence, mutations in the PALB2 gene are associated with breast cancer, pancreatic cancer and Fanconi anaemia. Women with a PALB2 mutation have an almost ten times higher risk of breast cancer than average. PALB2 mutations are the second most common cause of hereditary pancreatic cancer and biallelic mutations in the PALB2 gene are associated with the Fanconi anemia complementation group N and an increased risk of early onset cancer.

Epidemiology in the Arab World

View Map
Variant NameCountryGenomic LocationClinvar Clinical SignificanceCTGA Clinical Significance Condition(s)HGVS ExpressionsdbSNPClinvar
NM_024675.4:c.2014G>CLebanonchr16:23630140Benign, Likely BenignLikely PathogenicBreast CancerNG_007406.1:g.16218G>C; NM_024675.4:c.2014G>C; NP_078951.2:p.Glu672Gln45532440126630
NM_024675.4:c.2993G>ALebanonchr16:23622972Benign, Likely BenignAssociationBreast CancerNG_007406.1:g.23386G>A; NM_024675.4:c.2993G>A; NP_078951.2:p.Gly998Glu45551636126699
NM_024675.4:c.3350+4A>GLebanon; United Arab E...NC_000016.10:g.23607860T>CLikely Pathogenic, PathogenicLikely Pathogenic, PathogenicFanconi Anemia, Complementation group NNG_007406.1:g.38498A>G; NM_024675.4:c.3350+4A>G; NP_078951.2:p.?180177136126737
NM_024675.4:c.3464C>GUnited Arab EmiratesNC_000016.10:g.23603556G>CUncertain SignificanceUncertain SignificanceBreast CancerNG_007406.1:g.42802C>G; NM_024675.4:c.3464C>G; NP_078951.2:p.Ser1155Cys755609496402308

Other Reports

Saudi Arabia

Ghazwani et al. (2016) studied the underlying mutations affecting Fanconi anemia patients.  Ten patients, all from consanguineous families and of Saudi Arabian origin, were recruited.  Of these, 2 female infants were found to have a mutation in the PALB2 gene.  The first female had a strong family history of cancer. The second infant had a sister who had died from acute myeloid leukaemia secondary to FA.  A novel homozygous mutation in exon 13 of the PALB2 gene, c.3254del resulting in p.Leu1142Tyrfs*21, was detected in both patients.  This variant was not found in 50 ethnically-matched non FA controls and in-situ analysis predicted it to be disease causing.  Previous studies have found monoallelic loss of function mutations adjacent to this variant to be associated with an increased risk of breast cancer.  The study also found that unlike European FA cases, most Saudi FA mutations were in downstream FA pathway genes.  As the FANCD2 monoubiquitination assay does not screen for these genes, the assay was considered ineffective in diagnosing most Saudi FA cases. 

United Arab Emirates

In a retrospective study of breast cancer patients in the UAE, Altinoz et al (2020) identified two Emirati patients with pathogenic variants in the PALB2 gene. An additional six Emiratis were found to have variants of uncertain significance in the same gene.  

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